Preliminary Evidence for a Hormetic Effect on DNA Nucleotide Excision Repair in Veterans with Gulf War Illness
| Autor: | Kimberly Sullivan, Maria Abreu, Stefanie Sveiven, Nancy G. Klimas, Abdullah Alhamed, Ali Almutairy, Stephen G. Grant, Jean Johanna Latimer |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
DNA Repair DNA repair Lymphocyte exposure response 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Gene expression medicine Humans Persian Gulf Syndrome Gene 030304 developmental biology Veterans 0303 health sciences Messenger RNA business.industry Brief Report Public Health Environmental and Occupational Health Hormesis General Medicine DNA humanities Gulf War medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Immunology Gulf War Illness NER gene expression Female business Nucleotide excision repair |
| Zdroj: | Military Medicine |
| ISSN: | 1930-613X 0026-4075 |
| Popis: | IntroductionVeterans of the 1991 Gulf War were potentially exposed to a mixture of stress, chemicals and radiation that may have contributed to the persistent symptoms of Gulf War Illness (GWI). The genotoxic effects of some of these exposures are mediated by the DNA nucleotide excision repair (NER) pathway. We hypothesized that individuals with relatively low DNA repair capacity would suffer greater damage from cumulative genotoxic exposures, some of which would persist, causing ongoing problems.Materials and MethodsBlood samples were obtained from symptomatic Gulf War veterans and age-matched controls. The unscheduled DNA synthesis assay, a functional measurement of NER capacity, was performed on cultured lymphocytes, and lymphocyte mRNA was extracted and analyzed by sequencing.ResultsDespite our hypothesis that GWI would be associated with DNA repair deficiency, NER capacity in lymphocytes from affected GWI veterans actually exhibited a significantly elevated level of DNA repair (p = 0.016). Both total gene expression and NER gene expression successfully differentiated individuals with GWI from unaffected controls. The observed functional increase in DNA repair capacity was accompanied by an overexpression of genes in the NER pathway, as determined by RNA sequencing analysis.ConclusionWe suggest that the observed elevations in DNA repair capacity and NER gene expression are indicative of a “hormetic,” i.e., induced or adaptive protective response to battlefield exposures. Normally such effects are short-term, but in these individuals this response has resulted in a long-term metabolic shift that may also be responsible for the persistent symptoms of GWI. |
| Databáze: | OpenAIRE |
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